The drive to produce new generations of drug candidates is being expedited by the application of combinatorial chemistry, especially through the facilitated production of individual compounds or libraries by solid-phase mediated transformations. New templates, chemistries, and coding methods abound. Despite the fact that many organic reactions, especially those that involve electrophilic reagents, are incompatible with cross-linked polystyrene (a support which has been used for over thirty years for peptide synthesis), this material is still used for the vast majority of the chemistry. Preliminary feasibility experiments indicate that several fundamental organic transformations can be performed on the novel ASPECT/TM microporous polyethylene particulate support. A program is described to evaluate the usefulness of ASPECT for mediating C-C bond forming reactions; the examples include Friedel-Crafts acylations, Diels-Alder reactions and 1 ,3-dipolar additions. Systems have been selected involving consecutive transformations affording target molecules of potential pharmacological interest. Following completion of Phase I, Phase II will tune the particles, and their preparation, for commercialization; additionally screening of a selected library for factor Xa inhibition will be performed. PROPOSED COMMERCIAL APPLICATION: Commercialization of chemistry and instrumentation for automated organic synthesis is of enormous pharmaceutical and research interest, especially in the generation of molecular diversity libraries. At present the majority of syntheses are performed on polystyrene variants. The advent of a robust material applicable to a broad range of reactions and reagent treatments should measurably widen the scope of the method. Additionally, the extreme economy of the base polymer should markedly improve the economic viability of the technology. ASPECT materials formulated for organic synthesis are projected to take a 50% share of a 530 million market.